Fcγ receptors (FcγR) are cell surface receptors that bind the Fc region of immunoglobulin G (IgG) molecules. Among other functions, these receptors couple the formation of antibody-antigen complexes to effector cell responses. For example, cross-linking of activating Fcγ receptors by immune complexes can result in the phagocytosis of pathogens, killing of foreign and transformed cells by direct cytotoxicity, the clearance of toxic substances, and the initiation of an inflammatory response. Notably, the Fcγ receptors play a key role in autoimmunity. Autoantibody binding to activating Fc receptors triggers the pathogenic sequelae of autoimmune diseases such as idiopathic thrombocytopenic purpura, arthritis, systemic lupus erythrematosus, autoimmune hemolytic anemia, and others.
In humans and rodents there are three classes of Fcγ receptors, designated FcγRI, FcγRII, and FcγRIII (see, Ravetch and Bolland, 2001 Annual Rev. Immunol 19:275-90; and Ravetch and Kinet, 1991, Annual Rev. Immunol. 9:457-92). FcγRI sites are generally occupied by monomeric IgG, while RII and RIII receptors are generally unoccupied and available to interact with immune complexes. FcγRI, also called CD64, binds monomeric IgG with high affinity, and is present on monocytes and macrophages. FcγRII, also called CD32, binds to multimeric IgG (immune complexes or aggregated IgG) with moderate affinity, and is present on a variety of cell types, including B cells, platelets, neutrophils, macrophages and monocytes. FcγRIII, also called CD16, binds to multimeric IgG with moderate affinity and is the predominant activating FcγR on myeloid cells. FcγRIII is found in two forms. FcγRIIIA (CD16A), a transmembrane signaling form (50-65 kDa), is expressed by NK cells, monocytes, macrophages, and certain T cells. FcγRIIIB (CD16B), a glycosyl-phosphatidyl-inositol anchored form (48 kDa) form, is expressed by human neutrophils. See, e.g., Scallon et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86:5079-83 and Ravetch et al., 1989, J. Exp. Med. 170:481-97. Protein and nucleic acid sequences for CD16A are reported in Genbank as accession numbers P08637 (protein) and X52645 (nucleic acid) and in SWISS-PROT as accession number CAA36870. Protein and nucleic acid sequences for CD16B are reported in Genbank as accession numbers O75015 (protein) and X16863 (nucleic acid) and in SWISS-PROT as CAA34753.